Method for the express diagnosis of the physiological condition of a biological object and device for realizing the same

ABSTRACT

The present invention relates to a method that involves collecting a sample of biological liquid, placing the same in a cell ( 1 ) for analysis, supplying a current through the cell from a frequency- and amplitude-adjustable generator ( 2 ) and measuring the conductivity Y 1 . The method also involves using a biological-liquid reference ( 12 ) through which a current is supplied at the same amplitude and frequency before measuring its conductivity Yr. The method further involves calculating a value N 1 =Y 1 /Yr and the biological object is in a normal condition when N 1 &lt;1, whereas a potential disease is diagnosed when N 1 &gt;1. The device of the present invention comprises an analysis cell ( 1 ) having a generator ( 2 ) connected thereto and also includes a differential amplifier ( 3 ), a detector ( 4 ) and a measuring unit ( 5 ) connected in series. The differential amplifier ( 3 ) includes first and second current summing inputs ( 6, 7 ) and the generator ( 2 ) is connected to the first summing input ( 6 ) of said differential amplifier ( 3 ). An amplifier ( 8 ) is also n provided and has first and second current summing inputs ( 9, 10 ), while an electrode ( 13 ) is connected to the second summing input ( 7 ) of the differential amplifier ( 3 ) and is capable of three-dimensional displacement so as to be brought into contact with the biological liquid in the analysis cell ( 1 ) and with the reference ( 12 ). The detector ( 4 ) is connected to the measuring unit ( 5 ) through the first summing input ( 9 ) of the added amplifier ( 8 ), while a voltage regulator ( 11 ) is connected thereto through the second summing input ( 10 ) of said amplifier ( 8 ).

FIELD OF INVENTION

This invention relates to medicine and may be used as medical equipmentfor integral assessment of the condition of a human being or an animal

BACKGROUND OF THE INVENTION

Known in the art are methods for diagnosis of the physiologicalcondition of a biological object, which include collecting a sample of abiological fluid from a biological object and placing it in a cell foranalysis, passing an electrical current from a frequency and amplitudemodulated generator through the cell containing the biological fluid,measuring the impedance Y1 of the biological fluid sample, assessing thephysiological condition of the biological object under the sampleconductivity (U.S. Pat. No. 3,949,736; U.S. Pat. No. 4,038,975).

An advantage of the said method is that the impedance is measured with afrequency and amplitude modulated generator, which raises itsdescriptiveness.

A drawback of the said method is that the impedance is measured by apotential method, i.e., by registering voltages at a resistor dividingcircuit, which impairs the measurement accuracy. When measuringimpedances of biological fluids, the measurement accuracy is alsosignificantly influenced by the ambient conditions, such as the ambienttemperature, humidity, etc. The method provides for direct measurementsof the impedance values of a biological medium without any regard tothese factors. Moreover, a cell with a relatively large electrode areais used in the said method. Taking into account the fact that themeasured biological medium has air inclusions, the stationaryconstruction of the terminals and the cell does not allow to conductaccurate measurements for a long time interval, since in the course oftime the terminals are covered with an oxide film and the cellaccumulates the residues of the biological medium. The method does notprovide for express (within a very short time) diagnosis of thephysiological condition of a biological object by comparing the data onthe impedance of a sample with the reference data that is also changedunder the influence of the ambient atmosphere.

Also known in the art is a device for diagnosis of the physiologicalcondition of a biological object, which comprises a cell for placing abiological fluid therein, a generator connected to the analysis cell anda differential amplifier and a measuring means connected in series, thesaid analysis cell is made with the possibility of being connected tothe said differential amplifier (U.S. Pat. No. 1,387,980).

The said device also comprises a thermistor arranged in the cell, acurrent-to-voltage converter, a temperature compensator, a limitingamplifier, an analog-digital converter.

An advantage of the said device is the improved measurement accuracyowing to the monitoring and compensation of temperature-related factors.

The limitations of that technical solution are as follows: the devicemay be operated only at a fixed frequency and a fixed voltage of thegenerator, since the cell is included into the feedback loop of theamplifier, which leads to unstable operation of the circuit when theamplitude or the frequency of the generator is changed; the differentialamplifier is connected to the voltage terminals of the cell, whichadditionally impairs accuracy and contributes to unstable operation ofthe circuit at the selected operation mode of the device—subtraction ofvoltages; the construction of the cell and the circuit is complicateddue to the use of a thermistor and a current-to-voltage converter, atemperature compensator and an analog-digital converter; all thelimitations due to the use of a stationary cell and the terminals arepreserved, such as time-depended conductance of the terminals and theshell of the cell.

SUMMARY OF THE INVENTION

It is the primary object of this invention to provide a method fordiagnosis of the physiological condition of a biological object,according to which a sample is collected and a biological fluid isanalyzed so as to improve the functional capabilities, raise theaccuracy and objectivity of measurements with due regard to theinfluence of the ambient atmosphere and that of errors of measuringmeans to the analysis data, as well a create a device for diagnosis ofthe physiological condition of a biological object, wherein a generator,a differential amplifier and other technical means are made andinterconnected so as to enlarge the inventory of measuring means, raisethe accuracy and expand the range of measurements, improve theconvenience of operation and simplify the whole construction and, thus,to raise the quality and accuracy of measurements.

According to this invention, this object is achieved by improving theknown method of diagnosis of the physiological condition of a biologicalobject that involves collecting a sample of a biological fluid from thebiological object, placing the sample in an analysis cell, passing acurrent supplied by a frequency and amplitude modulated generatorthrough the analysis cell containing the biological fluid, and measuringthe conductivity Y1 of the biological fluid sample, which conductivityis served to assess the physiological condition of the biologicalobject, such improvement consists in that a biological fluid sample iscollected from a biological object after leaving the quiescent state andawakening, a reference biological fluid is additionally used, a currentof the same frequency and amplitude is passed through the referencebiological fluid and its conductivity Y_(R) is measured at constanttemperatures of the reference and the analysis cell containing thebiological fluid, the conductivity values Y1 and Y_(R) are compared bydetermining the ratio N₁=Y1/Y_(R), where N₁ lower than 1 evidences thenormal condition of the biological object and N₁ greater than 1 atteststo a disorder in the physiological condition of the biological object.

Some other embodiments of the method are possible wherein:

as the reference biological fluid a sample collected from a referencebiological object is used, which is placed in the reference cell similaras to its electrical parameters to the analysis cell; and theconductivity Y_(R) of the biological fluid sample contained in thereference cell is measured;

as the biological fluid reference a resistor is used that has theconductivity equal to that of the biological fluid and the analysiscell;

a second sample is collected from the biological object in the wake timebefore the first meal and is placed in an additional analysis cellsimilar as to its electrical parameters to the said analysis cell, theconductivity Y2 of the second sample is measured, the ratio N₂=Y2/Y_(R)is determined by the biological fluid conductivity in the additionalanalysis cell (18) and that in the reference cell, and the condition ofthe immune system is assessed by the compliance with the relationN₁/N₂>1, where at the value N₁<1 the immune system activity grows, butif N₁ approaches to 1 it is reduced;

saliva is used as the biological fluid;

urea is used as the biological fluid;

blood is used as the biological fluid.

The object of this invention is also attained owing to that the knowndevice for the diagnosis of the physiological condition of a biologicalobject contains the analysis cell intended for placing a biologicalfluid therein, a generator connected to the analysis cell and adifferential amplifier, a detector and a measuring unit connected inseries, the said analysis cell being made with the possibility of beingconnected to the differential amplifier; according to the invention, thedifferential amplifier is made with first and second current summinginputs, the generator is connected to the first summing input of thedifferential amplifier, additionally introduced are an amplifier havingthe first and the second summing inputs, a voltage regulator, areference cell intended for placing a reference biological fluid intoit, an electrode connected to the second summing input and made with thepossibility of its spatial displacement for making contact with thebiological fluid in the analysis cell and the reference cell, thedetector being connected to the measuring unit through the first summinginput of the amplifier and the voltage regulator being connected theretothrough the second summing input of the amplifier.

Some other embodiments of the invention are possible, where:

an equivalent of the electrode is introduced that is made in the form ofa resistor with the conductivity equal to that of the terminal andconnected to the second summing input of the differential amplifierthrough a switch;

the generator is made as the output signal frequency and amplitudemodulated unit;

the electrode is made as a coaxial probe with the cone-shaped tip.

Owing to the introduction of the reference cell, comparison of thecharacteristics of the biological fluid to the reference biologicalfluid as well as due to making the device in accordance with theabove-said construction features having functional links therebetween,the object of the invention has been attained.

The said advantages as well as the features of this invention areexplained by its best embodiment with references to the appendedFigures. Since the method is realized while the device is operated, thedescription of the method, as the subject of the invention, is given inthe section where the operation of the device is described.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a functional block-diagram of the device.

FIG. 2 shows the construction of the electrode made in the form of aprobe.

DESCRIPTION OF THE BEST EMBODIMENT

The device for diagnosis of the physiological condition of a biologicalobject (FIG. 1) comprises the analysis cell 1 intended for placing abiological fluid into it. The generator 2 is connected to the cell 1.The differential amplifier 3, the detector 4, the measuring unit 5 areconnected in series. The cell 1 is made so as to allow its connection tothe differential amplifier 3.

The differential amplifier 3 is made with the first and the secondcurrent summing inputs, 6 and 7, respectively. The generator 2 isconnected to the first summing input 6 of the differential amplifier 3.The amplifier 8 is made with the first and the second summing inputs, 9and 10, respectively. The device is provided with the voltage regulator11 and the biological fluid reference 12. The electrode 13 is connectedto the second summing input 7 of the differential amplifier 3 and madeso as to allow its spatial displacement for making contact with abiological fluid in the analysis cell 1 and with the reference 12. Thedetector 4 is connected to the measuring unit 5 through the firstsumming input of the amplifier 8. The regulator 11 is connected to themeasuring unit 5 through the second summing input of the amplifier 8.

As the reference 12 a biological fluid sample collected from a referencebiological object (an earlier diagnosed healthy human being or animal)may be used, which is placed into the reference cell similar as to itselectrical parameters to the analysis cell 1, after which theconductivity Y_(R) of the biological fluid sample is measured in thereference cell. Or, as the reference 12 a resistor may be used that hasa conductivity equal to that of the biological fluid in the referencecell containing a biological fluid. Also, as the reference 12, a set ofresistors may be used for investigating various biological fluids, suchas saliva, blood, urea.

The device may be supplemented with an equivalent of the electrode 13,which is made in the form of the resistor 14 having the conductivityequal to that of the electrode 13 and connected to the second summinginput 7 of the differential amplifier 3 through a switch 15, whichenables to allow for errors introduced directly by the electrode 13.

The generator 2 may be made capable of modulating the output signalfrequency and amplitude, for which purpose it comprises a frequencyregulator 16 and an attenuator 17 for amplitude modulation. Theintroduction of the frequency regulator 16 and the attenuator 17 enablesto additionally improve the measurement accuracy due to conductingmeasurements in a resonance mode.

To further improve the measurement accuracy, the electrode 13 (FIG. 2)may be made in the form of a coaxial probe with the cone-shaped tip,which enables to conduct measurements in a definite point, promptlyclear it from biological fluids and exclude the effect of air bubbles inthe near-electrode conical layer in the course of putting the probe intoa biological fluid. Such a probe may be connected to the second input 7of the differential amplifier 3 with a coaxial cable.

The making of the differential amplifier 3 with the first and the secondcurrent summing inputs 6 and 7 as well as the introduction of theamplifier 8 (all a differential one) with the first and the secondcurrent summing inputs 9 and 10 enables to preclude errors associatedwith potential measurements and constantly monitor the parameters of theelectrode 13, and to compensate or eliminate measurement errors beforemeasuring. The connection of the second summing input of the amplifier 8with the regulator 11 enables to eliminate the effect of the signaldirect component, extract and amplify the useful signal only, thussignificantly expanding the range of measurements.

The device (FIG. 1) operates as follows.

First, a biological fluid sample is collected from a biological object(a human being or an animal), which is then placed in the analysis cell1. A current supplied by the generator 2, which frequency and amplitudeis modulated by the frequency regulator 16 and the attenuator 17, ispassed through the cell 1. The conductivity Y1 is measured by themeasuring unit 5. A biological fluid sample is collected from abiological object (a human being or an animal) just after his/itsawakening, in the period when, as research show, the conductivity Y1 isthe closest to the conductivity Y_(R) of the reference 12, or slightlylower. A current of the same frequency and amplitude is passed throughthe reference 12 and its conductivity Y_(R) is measured. Theconductivity Y1 of the biological fluid in the cell land that of thereference 12 by determining their ratio N₁=Y1/Y_(R). If the value N₁ isless than 1, it evidences the normal condition of the biological object,but if it exceeds 1, it attests to a possible disease and a disorder ofthe physiological condition of the biological object. The furtherdiagnosis of a disease is made by customary methods. The value of theelectrical conductivity obtained in the first measurement is, as studiesshowed, in proportion to the maximum accumulation of alien components inthe biological fluid.

For further express diagnosis the second biological fluid sample iscollected from the biological object before the first meal (usually in0.5-1 hour after awakening). The biological fluid is placed in theadditional analysis cell 18 (FIG. 1) that is similar as to its electricparameters to the said cell 1. The conductivity Y2 of the second sampleis measured. The conductivity Y2 of the biological fluid in theadditional analysis cell 18 and the conductivity Y of the reference 12by determining their ratio N₂=Y2/Y_(R). The condition of the immunesystem of the biological object is determined by compliance with thevalue 1<N₁/N₂; if the value of N₂<1, then the activity of the immunesystem grows (the normal condition of the biological object's immunesystem is diagnosed), but if the value of N₂ approaches to 1 from leftor right (0.95<N₂<2.1), the activity of the immune system decreases (apossible disease of the immune system is diagnosed). The furtherdiagnosis of a disease is made by customary methods. The value of theelectrical conductivity obtained in the first measurement is, as studiesshowed, in proportion to the resistance of the biological object toexternal factors, and the relation between the first measurement and thesecond measurement upon expiration of the said time period characterizesthe reaction of the biological object to the influence of externalfactors.

Since the measurements are conducted with the same probe in the similarambient conditions (temperature, humidity, pressure, etc.) for theobject under study, and the reference and the relation between themeasured parameters is determined, random errors do not practicallyinfluence the studies and systematic errors are compensated owing to theproposed circuit design.

It is most advisable to use saliva as the biological fluid for expressdiagnosis, since it is the most descriptive and easy-to-collectbiological fluid of a biological object, which is the easiest forstudying by the proposed method. The specific resistance of the humansaliva (without accounting for the resistance of the casing of the cell1) for the reference 12 is 3.238 Ohm·m.

But, the method does not preclude the use of urea as a biological fluid(specific resistance is 2.08 Ohm·m) as well as blood (specificresistance is 1.62 Ohm·m).

When implementing the method, for the purpose of improving the accuracy,it is advisable to introduce an equivalent of the electrode 13, which isto be made in the form of a resistor 14 with the conductivity equal tothat of the electrode 13. In such a case the electrode 13 is wiped dryand first left in the air, without introducing it into the cell 1. Theregulator 11 is set in the neutral position. When the switch 15 islocked, the equivalent of the electrode 13, i.e., the resistor 14, isconnected to the second summing input 7 of the differential amplifier 3.Upon summing, the resulting basic signal is fed to the measuring unit 5from the generator 2 and through the first summing input of thedifferential amplifier 3, the detector 4 and the amplifier 8. Theconductivity value Yset₁ is set at the measuring unit 5 with theregulator 11. The switch 15 is unlocked, and the electrode 13 is placedon the reference 12. When the conductivity value Yset₂, different fromYset₁, is obtained at the measuring unit 5, the measurement error, whichis additionally introduced by the electrode 13, is evaluated by thedifference between the two values. Thus, in the course of measuringconductivities of biological fluids it is always possible to take intoaccount the time changes in the error introduced by the electrode 13due, e.g., to oxidization of its contact surface.

In case the conductivity of a biological fluid is to be measured, theprobe, i.e., the electrode 13, is brought into contact with thereference 12. For the purpose of making the measurement of theconductivity Y_(R) stable the needed value of the output signal as tofrequency and amplitude is selected with the frequency regulator 16 andthe attenuator 17, thus setting the reference point. Then the sharpconical probe tip of the electrode 13 is brought into contact with thesurface of the biological fluid in the analysis cell 1. The valueproportional to the conductivity Y1 of the biological medium is recordedat the measuring unit 5. After this, as stated above, their relation isdetermined.

When measuring biological fluids, which are characterized by a lowinformation signal and a high common signal, the attenuator 17 is set,in the course of adjusting it on the reference 12, in the position thatcorresponds to the maximum level of the output signal from the generator2; and a new reference point is set with the voltage regulator 11 at themeasuring unit 5 for measuring the conductivity of another biologicalfluid.

Example 1. Studied were blood, urea and saliva collected from patientswith the grave condition of the respiratory system in the complicationperiod. The values obtained were: N₁=1.5−2.1; N₂=1.6−2.2.

Example 2. A group of 27 sportsmen was studied. In the future 6 personsfrom the group were ill with influenza. The analyses conducted inaccordance with the claimed method showed that for those 6 persons thevalue N₁ before the disease was in the range from 1.0 to 1.4, i.e., theactivity of the immune system proved to be lowered, and in the futurethey had the said infection disease. For the rest members of the groupthe value N₂ was from 0.6 to 0.8, and the followed up persons had notgot any diseases during the infectious period.

Example 3. The effects of external factors, such as high radiationbackground, excessive physical loads, over-eating, food-poisoning,troubled sleep, stress, etc, on the physiological condition of humanbeings were studied. For most negative factors stated above the valuesN₁ and N₂ were from 1.1 to 1.6; poisoning with nitrate-containingfoodstuffs was characterized by values from 1.8 to 2.1.

Example 4. Various diseases of the urogenital system were studied. Thevalue N₂ after surgery was 1.8 to 2.0; in a week after surgery—1.2-1.4.

Example 5. A group of 3 persons having the values N₁ and N₂ slightlyexceeding 1 was followed up for 10 months. The studies showed that in acase where these values, especially N₂, are preserved at the level of1.1-1.3 for more than 30 days, various diseases of the locomotorapparatus and the blood circulation system began to appear.

INDUSTRIAL APPLICABILITY

The claimed method of express diagnosis and device for realizing samemay be most successfully used in medicine for integral assessment of thephysiological condition of a human being or an animal.

What is claimed is:
 1. A method of diagnosis of the physiologicalcondition of a biological object, which involves collecting a biologicalfluid sample from a biological object, placing the sample in an analysiscell (1), passing an alternating current through the cell (1) for theanalysis with a biological liquid, and measuring the biological fluidsample conductivity Y1 used for assessment of the physiologicalcondition of the biological object, wherein the biological fluid sampleis collected from the biological object after awakening, a reference(12) biological fluid is additionally used, an alternating current ofthe same frequency and amplitude is passed through the referencebiological fluid (12) and its conductivity Y_(R) is measured at constanttemperatures of the reference and the analysis cell (1) containing thebiological fluid, the conductivity values Y1 and Y_(R) are compared bydetermining the ratio N₁=Y1/Y_(R), where N₁ lower than 1 evidences thenormal condition of the biological object and N₁ greater than 1 atteststo a disorder in the physiological condition of the biological object.2. The method according to claim 1, wherein the biological fluid samplecollected from a reference biological object and used as the biologicalfluid reference (12) is placed in the reference cell is similar as toits electrical parameters to the analysis cell, and the conductivityY_(R) of the biological fluid sample contained in the reference cell ismeasured.
 3. The method according to claim 1, wherein a resistor is usedas the biological fluid reference (12), which has the conductivity equalto that of the biological fluid and the analysis cell.
 4. The methodaccording to claim 1, wherein a second biological fluid sample iscollected from the biological object before a first meal and is placedin an additional analysis cell (18) similar as to its electricalparameters to the said analysis cell (1), the conductivity Y2 of thesecond sample is measured, the ratio N₂=Y2/Y_(R) is determined by thebiological fluid conductivity in the additional analysis cell (18) andthat in the reference cell, and the condition of the immune system isassessed by the compliance with the relation N₁/N₂>1, where at the valueN₁<1 the immune system activity grows, but if N₁ approaches to 1 it isreduced.
 5. The method according to claim 1, wherein saliva is used asthe biological fluid.
 6. The method according to claim 1, wherein ureais used as the biological fluid.
 7. The method according to claim 1,wherein blood is used as the biological fluid.
 8. A device for diagnosisof the physiological condition of a biological object comprising ananalysis cell (1) intended for placing a biological fluid therein, analternating current generator (2) connected to the cell (1), and adifferential amplifier (3), a detector (4), a measuring unit (5) thatare connected in series, the cell (1) being made so as to allow itsconnection to the differential amplifier (3), wherein the differentialamplifier (3) is made with first (6) and second (7) current summinginputs and providing summation on the mentioned current summing inputs(6), (7), the alternating current generator (2) is connected to thefirst summing input (6) of the differential amplifier; furthercomprising an amplifier (8), which is made with first and the secondsumming inputs (9), (10) and providing summation on the mentioned inputs(9), (10), a voltage regulator (11), a biological fluid reference (12),an electrode (13) connected to the second summing input (7) of thedifferential amplifier (3) and made so as to allow spatial displacementof the electrode for making alternate contact with the analysis cell (1)for analysis or with the biological fluid reference (12), the detector(4) being connected to the measuring unit (5) through the first input(9) of the amplifier (8) and the voltage regulator (11) being connectedthereto through the second input (10) of the amplifier (8).
 9. Thedevice according to claim 8, further comprising a correspondent to theelectrode (13), which is made in the form of a resistor (14) having theconductivity equal to that of the electrode (13) and connected to thesecond input (7) of the differential amplifier (3) through a switch(15).
 10. The device according to claim 8, wherein the generator (2) ismade capable of modulating the output signal frequency and amplitude.11. The device according to claim 8, wherein the electrode (13) is madein the form of a coaxial probe with the cone-shaped tip.